OBJECTIVES: This is a continuation of our research program to elucidate the biosynthetic pathway to anthramycin, determine the structure of the anthramycin-DNA adduct, and determine the biological consequences of DNA damage. APPROACH: Utilizing stable isotope labelled precursors (13C, 15N, 2H) in combination with 1H and 13C-NMR we are determining the labelling pattern of tyrosine and tryptophan in anthramycin. Isolated DNA, chromatin and synthetic polydeoxynucleotides will be used to determine the structure of the drug-DNA adducts. 1H and 13C-NMR will be used to monitor points of covalent and hydrogen bonding between the drugs and DNA. Using mammalian cells we will characterize the DNA damage and its repair. Both normal and repair deficient (XP and AT cell lines) will be used and we will estimate the following DNA repair parameters: single strand breaks, unscheduled DNA synthesis, excision removal of drug, ligation and cell survival.